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Experimental and Toxicologic Pathology 59 (2008) 415–423 www.elsevier.de/etp

Apoptotic effect of organophosphorus insecticide chlorpyrifos on mouse retina in vivo via oxidative stress and protection of combination of vitamins C and E
Fu Yua,b, Ziren Wanga,Ã, Bao Jua, Yongqiang Wanga, Jing Wanga, Decheng Baic
a

School of Life Sciences, Lanzhou University, Lanzhou730000, PR China Shenzhen Seventh People’s Hospital, Shenzhen, PR China c School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China
b

Received 19 September 2007; accepted 20 November 2007

Abstract
Organophosphorus insecticide poisoning is widely investigated, and a growing number of evidence indicates its effects to cause ocular lesions, but the mechanisms of its ocular effects arenot well elucidated. Here, effects of organophosphorus insecticide chlorpyrifos on mouse retina in vivo and protection of combination of vitamins C and E were reported. Cell apoptosis, lipid peroxidation and DNA damage were increased, and activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were decreased in retina of chlorpyrifosadministrated mice (63mg/kg, single treatment, via oral gavage). Pretreatment of combination of antioxidants vitamin C (250 mg/kg) and vitamin E (150 mg/kg) (once daily for 6 days, hypodermic injecting) significantly attenuated these effects of chlorpyrifos, demonstrating oxidative stress was involved in chlorpyrifos-induced cell apoptosis in mouse retina. Moreover, chlorpyrifos treatment inhibited acetylcholinesteraseactivity and promoted [Ca2+]i level in mouse retinal cells, which were also attenuated by combination of vitamins C and E. These results may have implications for treatment of organophosphorus insecticide poisoning in retina with combination of vitamins C and E. r 2007 Elsevier GmbH. All rights reserved.
Keywords: Organophosphorus insecticide; Retina; Oxidative stress; Chlorpyrifos; Vitamin C; VitaminE

Introduction
Organophosphorus insecticides are widely used in agriculture or for other purposes. For example, as one of the most widely used organophosphorus insecticides in the United States, chlorpyrifos [O,O-diethyl-O-(3,5, 6-trichloro-2-pyridyl)-phosphorothioate] had an annual usage of 8–10 million pounds in the agricultural sector in 1999, according to the US Environmental ProtectionÃCorresponding author. Tel./fax: +86 931 8912561.

E-mail address: wangzr@lzu.edu.cn (Z. Wang). 0940-2993/$ - see front matter r 2007 Elsevier GmbH. All rights reserved. doi:10.1016/j.etp.2007.11.007

Agency, and it is contained within approximately 800 registered products on the market for a number of purposes, including indoor pest control, and pest control for a variety of food crops,ornamental plants, greenhouses and sod (Lee et al., 2004). The widespread use of organophosphorus insecticides, however, brings high risks of severe health problems. Besides occupational poisoning in industrial production and agricultural application, instances of acute organophosphorus insecticide poisoning also include suicide, homicide and accidental overdose (Kamiya et al., 2001; Zhou et al., 2002;Kallel et al., 2007). It is generally

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416 F. Yu et al. / Experimental and Toxicologic Pathology 59 (2008) 415–423

assumed that, as inhibitors of cholinesterase activity, organophosphorus insecticides produce overstimulation of cholinergic neurotransmission, eliciting signs and symptoms such as increased salivation, sweating, changes in blood pressure and heart rate,nausea, diarrhea, confusion, headache, muscle tremor, and in more severe situation, breathing difficulty, convulsions or even death (Padilla et al., 2005). Japanese studies from the 1960s and 1970s demonstrated that organophosphorus insecticide-exposed humans developed chronic ocular degeneration, first suggesting that exposure to organophosphorus insecticides might lead to ocular damage (Boyes et al.,...
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